Functional connectome hierarchy of thalamus impacts fatigue in acute stroke patients.

This study aimed to explore the topographic features of thalamic subregions, functional connectomes and hierarchical organizations between thalamus and cortex in poststroke fatigue patients. We consecutively recruited 121 acute ischemic stroke patients (mean age: 59 years) and 46 healthy controls matched for age, sex, and educational level. The mean age was 59 years (range 19-80) and 38% of acute stroke patients were females. Resting-state functional and structural magnetic resonance imaging were conducted on all participants. The fatigue symptoms were measured using the Fatigue Severity Scale. The thalamic functional subdivisions corresponding to the canonical functional network were defined using the winner-take-all parcellation method. Thalamic functional gradients were derived using the diffusion embedding analysis. The results suggested abnormal functional connectivity of thalamic subregions primarily located in the temporal lobe, posterior cingulate gyrus, parietal lobe, and precuneus. The thalamus showed a gradual increase from the medial to the lateral in all groups, but the right thalamus shifted more laterally in poststroke fatigue patients than in non- poststroke fatigue patients. Poststroke fatigue patients also had higher gradient scores in the somatomotor network and the right medial prefrontal and premotor thalamic regions, but lower values in the right lateral prefrontal thalamus. The findings suggested that poststroke fatigue patients had altered functional connectivity and thalamocortical hierarchical organizations, providing new insights into the neural mechanisms of the thalamus.

Structural MRI measures are associated with fatigue severity and persistence in a large, real-world cohort of people with multiple sclerosis.

BACKGROUND: Results of research on radiological hallmarks of multiple sclerosis (MS) fatigue have been conflicting. OBJECTIVE: To investigate the associations of lesion and brain compartment volumes with fatigue severity and persistence in people with multiple sclerosis (PwMS). METHODS: The Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS) network collects standardized data during routine care of PwMS from 10 healthcare institutions. Magnetic resonance imaging (MRI) predictors included baseline brain parenchymal (BPF) and gray matter fractions (GMF) and T2 lesion volume (T2LV). The Quality of Life in Neurological Disorders (Neuro-QOL) fatigue subscore was analyzed linearly and categorically using T-score cutpoints, with a period of elevated symptoms defined as T-score ⩾ mean + 0.5 SD over follow-up. RESULTS: At baseline, of 4012 participants (average age: 45.6 ± 11.8 years; 73% female; 31% progressive MS), 2058 (51%) had no fatigue, 629 (16%) had mild fatigue, and 1325 (33%) had moderate-to-severe fatigue. One SD greater baseline BPF and GMF were associated with 0.83 (p < 0.001) and 0.38 (p = 0.02) lower values in the baseline Neuro-QOL fatigue T-score. A 1 SD lower log of total T2LV was associated with a 0.49 (p < 0.001) lower baseline fatigue T-score. Higher BPF and lower T2LV at baseline were associated with lower odds of subsequent periods of elevated fatigue. CONCLUSION: Baseline lesion burden and lower generalized whole-brain volumes were associated with MS fatigue in cross-sectional and longitudinal analyses in a large, real-world cohort of PwMS.

Mirror movements in multiple sclerosis -a clinical, electrophysiological, and imaging study.

BACKGROUND: Mirror movements (MM) are commonly caused by a defect of interhemispheric pathways also affected in multiple sclerosis (MS), particularly the corpus callosum. We investigated the prevalence of MM in MS in relation to functional and morphological callosal fiber integrity by transcranial magnetic stimulation (TMS), magnetic resonance imaging (MRI), as well as fatigue. METHODS: In 21 patients with relapsing-remitting MS and 19 healthy controls, MM were assessed and graded (Woods and Teuber scale: MM 1-4) using a bedside test. Fatigue was evaluated using the Fatigue Scale for Motor and Cognitive Functions (FSMC) questionnaire. TMS measured ipsilateral silent period latency and duration. MRI assessed callosal atrophy by measuring the normalized corpus callosum area (nCCA), corpus callosum index (CCI), and lesion volume. RESULTS: MS patients had significantly more often and pronounced MM compared to healthy controls (p = 0.0002) and nCCA was significantly lower (p = 0.045) in MRI studies. Patients with higher MM scores (MM > 1 vs. MM 0/1) showed significantly more fatigue (higher FSMC sum score, p = 0.04, motor score, p = 0.01). In TMS and MRI studies, no significant differences were found between patients with MM 0/1 and those with MM > 1 (ipsilateral silent period measurements, CCA, CCI and lesion volume). CONCLUSIONS: MM are common in MS and can easily be detected through bedside testing. As MM are associated with fatigue, they might indicate fatigue in MS. It is possible that other cerebral structures, in addition to the corpus callosum, may contribute to the origin of MM in MS.

Frontal-striatal glucose metabolism and fatigue in patients with multiple sclerosis, long COVID, and COVID-19 recovered controls.

This study compared brain glucose metabolism using FDG-PET in the caudate nucleus, putamen, globus pallidus, thalamus, and dorsolateral prefrontal cortex (DLPFC) among patients with Long COVID, patients with fatigue, people with multiple sclerosis (PwMS) patients with fatigue, and COVID recovered controls. PwMS exhibited greater hypometabolism compared to long COVID patients with fatigue and the COVID recovered control group in all studied brain areas except the globus pallidus (effect size range 0.7-1.5). The results showed no significant differences in glucose metabolism between patients with Long COVID and the COVID recovered control group in these regions. These findings suggest that long COVID fatigue may involve non-CNS systems, neurotransmitter imbalances, or psychological factors not captured by FDG-PET, while MS-related fatigue is associated with more severe frontal-striatal circuit dysfunction due to demyelination and neurodegeneration. Symmetrical standardized uptake values (SUVs) between hemispheres in all groups imply that fatigue in these conditions may be related to global or network-level alterations rather than hemisphere-specific changes. Future studies should employ fine-grained analysis methods, explore other brain regions, and control for confounding factors to better understand the pathophysiology of fatigue in MS and long COVID. Longitudinal studies tracking brain glucose metabolism in patients with Long COVID could provide insights into the evolution of metabolic patterns as the condition progresses.

Subcortical Volumes as Early Predictors of Fatigue in Multiple Sclerosis.

OBJECTIVE: Fatigue is a frequent and severe symptom in multiple sclerosis (MS), but its pathophysiological origin remains incompletely understood. We aimed to examine the predictive value of subcortical gray matter volumes for fatigue severity at disease onset and after 4 years by applying structural equation modeling (SEM). METHODS: This multicenter cohort study included 601 treatment-naive patients with MS after the first demyelinating event. All patients underwent a standardized 3T magnetic resonance imaging (MRI) protocol. A subgroup of 230 patients with available clinical follow-up data after 4 years was also analyzed. Associations of subcortical volumes (included into SEM) with MS-related fatigue were studied regarding their predictive value. In addition, subcortical regions that have a central role in the brain network (hubs) were determined through structural covariance network (SCN) analysis. RESULTS: Predictive causal modeling identified volumes of the caudate (s [standardized path coefficient] = 0.763, p = 0.003 [left]; s = 0.755, p = 0.006 [right]), putamen (s = 0.614, p = 0.002 [left]; s = 0.606, p = 0.003 [right]) and pallidum (s = 0.606, p = 0.012 [left]; s = 0.606, p = 0.012 [right]) as prognostic factors for fatigue severity in the cross-sectional cohort. Moreover, the volume of the pons was additionally predictive for fatigue severity in the longitudinal cohort (s = 0.605, p = 0.013). In the SCN analysis, network hubs in patients with fatigue worsening were detected in the putamen (p = 0.008 [left]; p = 0.007 [right]) and pons (p = 0.0001). INTERPRETATION: We unveiled predictive associations of specific subcortical gray matter volumes with fatigue in an early and initially untreated MS cohort. The colocalization of these subcortical structures with network hubs suggests an early role of these brain regions in terms of fatigue evolution. ANN NEUROL 2022;91:192-202.

MRI Assessment of Cerebral Blood Flow in Nonhospitalized Adults Who Self-Isolated Due to COVID-19.

BACKGROUND: Neurological symptoms associated with coronavirus disease 2019 (COVID-19), such as fatigue and smell/taste changes, persist beyond infection. However, little is known of brain physiology in the post-COVID-19 timeframe. PURPOSE: To determine whether adults who experienced flu-like symptoms due to COVID-19 would exhibit cerebral blood flow (CBF) alterations in the weeks/months beyond infection, relative to controls who experienced flu-like symptoms but tested negative for COVID-19. STUDY TYPE: Prospective observational. POPULATION: A total of 39 adults who previously self-isolated at home due to COVID-19 (41.9 ± 12.6 years of age, 59% female, 116.5 ± 62.2 days since positive diagnosis) and 11 controls who experienced flu-like symptoms but had a negative COVID-19 diagnosis (41.5 ± 13.4 years of age, 55% female, 112.1 ± 59.5 since negative diagnosis). FIELD STRENGTH AND SEQUENCES: A 3.0 T; T1-weighted magnetization-prepared rapid gradient and echo-planar turbo gradient-spin echo arterial spin labeling sequences. ASSESSMENT: Arterial spin labeling was used to estimate CBF. A self-reported questionnaire assessed symptoms, including ongoing fatigue. CBF was compared between COVID-19 and control groups and between those with (n = 11) and without self-reported ongoing fatigue (n = 28) within the COVID-19 group. STATISTICAL TESTS: Between-group and within-group comparisons of CBF were performed in a voxel-wise manner, controlling for age and sex, at a family-wise error rate of 0.05. RESULTS: Relative to controls, the COVID-19 group exhibited significantly decreased CBF in subcortical regions including the thalamus, orbitofrontal cortex, and basal ganglia (maximum cluster size = 6012 voxels and maximum t-statistic = 5.21). Within the COVID-19 group, significant CBF differences in occipital and parietal regions were observed between those with and without self-reported on-going fatigue. DATA CONCLUSION: These cross-sectional data revealed regional CBF decreases in the COVID-19 group, suggesting the relevance of brain physiology in the post-COVID-19 timeframe. This research may help elucidate the heterogeneous symptoms of the post-COVID-19 condition. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 3.

Brain morphometry changes with fatigue severity in fibromyalgia.

OBJECTIVES: This study investigated brain morphometry changes associated with fatigue severity in fibromyalgia (FM). METHODS: Clinical profiles and brain-MRI data were collected in patients with FM. Patients were divided into three groups based on their fatigue severity. Using voxel-based morphometry analysis and trend analysis, neural substrates showing volumetric changes associated with fatigue severity across the three groups were identified. Their seed-to-voxel structural covariance (SC) networks with the whole brain were studied in distribution and strength. RESULTS: Among the 138 enrolled patients with FM, 23, 57, and 58 were categorised into the mild, moderate, and severe fatigue groups, respectively. The number of musculoskeletal pain regions and intensity of pain were not associated with fatigue severity, but somatic symptoms and psychiatric distress, including waking unrefreshed, depression, and anxiety, were associated with fatigue severity. After adjusting for anxiety and depression, decreased bilateral thalamic volumes were associated with higher fatigue severity. The SC distributions of the thalamic seed were more widespread to the frontal, parietal, subcortical, and limbic regions in patients with higher fatigue severity. In addition, increased right inferior temporal cortex volumes were associated with higher fatigue severity. The SC distributions of the right inferior temporal seed were more over the temporal cortex and the SC strengths of the seed were higher with the bilateral occipital cortex in patients with higher fatigue severity. CONCLUSIONS: The thalamus and the right inferior temporal cortex are implicated in the manifestation of fatigue severity in FM. Future therapeutic strategies targeting these regions are worthy of investigation.

Multisensory mental imagery of fatigue: Evidence from an fMRI study.

Functional imaging experimental designs measuring fatigue, defined as a subjective lack of physical and/or mental energy characterizing a wide range of neurologic conditions, are still under development. Nineteen right-handed healthy subjects (9 M and 10 F, mean age 43.15 ± 8.34 years) were evaluated by means of functional magnetic resonance imaging (fMRI), asking them to perform explicit, first-person, mental imagery of fatigue-related multisensory sensations. Short sentences designed to assess the principal manifestations of fatigue from the Multidimensional Fatigue Symptom Inventory were presented. Participants were asked to imagine the corresponding sensations (Sensory Imagery, SI). As a control, they had to imagine the visual scenes (Visual Imagery, VI) described in short phrases. The SI task (vs. VI task) differentially activated three areas: (i) the precuneus, which is involved in first-person perspective taking; (ii) the left superior temporal sulcus, which is a multisensory integration area; and (iii) the left inferior frontal gyrus, known to be involved in mental imagery network. The SI fMRI task can be used to measure processing involved in mental imagery of fatigue-related multisensory sensations.

Structural Basal Ganglia Correlates of Subjective Fatigue in Middle-Aged and Older Adults.

OBJECTIVE: Fatigue is among the most common complaints in community-dwelling older adults, yet its etiology is poorly understood. Based on models implicating frontostriatal pathways in fatigue pathogenesis, we hypothesized that smaller basal ganglia volume would be associated with higher levels of subjective fatigue and reduced set-shifting in middle-aged and older adults without dementia or other neurologic conditions. METHODS: Forty-eight non-demented middle-aged and older adults (Mage = 68.1, SD = 9.4; MMMSE = 27.3, SD = 1.9) completed the Fatigue Symptom Inventory, set-shifting measures, and structural MRI as part of a clinical evaluation for subjective cognitive complaints. Associations were examined cross-sectionally. RESULTS: Linear regression analyses showed that smaller normalized basal ganglia volumes were associated with more severe fatigue (ß = -.29, P = .041) and poorer Trail Making Test B-A (TMT B-A) performance (ß = .30, P = .033) controlling for depression, sleep quality, vascular risk factors, and global cognitive status. Putamen emerged as a key structure linked with both fatigue (r = -.43, P = .003) and TMT B-A (ß = .35, P = .021). The link between total basal ganglia volume and reduced TMT B-A was particularly strong in clinically fatigued patients. CONCLUSION: This study is among the first to show that reduced basal ganglia volume is an important neurostructural correlate of subjective fatigue in physically able middle-aged and older adults without neurological conditions. Findings suggest that fatigue and rapid set-shifting deficits may share common neural underpinnings involving the basal ganglia, and provide a framework for studying the neuropathogenesis and treatment of subjective fatigue.

Neuroimaging correlates of persistent fatigue in older adults: A secondary analysis from the Multidomain Alzheimer Preventive Trial (MAPT) trial.

OBJECTIVES: Fatigue has been suggested as a marker of biological aging. It seems plausible that this symptom might be associated with changes in brain health. The objective of this study was to examine the associations between persistent fatigue and neuroimaging correlates in a non-disease-specific population of community-dwelling older adults. METHODS: We performed a cross-sectional analysis using data from The Multidomain Alzheimer Preventive Trial (MAPT). We included 458 subjects. Persistent fatigue was defined as meeting exhaustion criterion of Fried frailty phenotype in two consecutive clinical visits six months apart between study baseline and one year. Brain imaging correlates, assessed by magnetic resonance imaging (MRI), were the outcomes. The associations between persistent fatigue and brain correlates were explored using mixed model linear regressions with random effect at the center level. RESULTS: The mean age of the participants was 74.8 ± 4 years old, and 63% of the subjects were women. Forty-seven participants (10%) exhibited a persistent fatigue profile. People with persistent fatigue were older compared to subjects without persistent fatigue (76.2 years ± 4.3 vs.74.7 ± 3.9 p = 0.009). Persistent fatigue was associated with higher white matter hyperintensity volume in the fully adjusted analysis. We did not find any cross-sectional association between persistent fatigue and sub-cortical volumes and global and regional cortical thickness. CONCLUSION: Persistent fatigue was cross-sectionnally associated with higher white matter hyperintensity volume in older adults. Further longitudinal studies, using an assessment tool specifically designed and validated for measuring fatigue, are needed to confirm our findings.

Meningoencephalitis associated with COVID-19: a systematic review.

With the growing number of COVID-19 cases in recent times. significant set of patients with extra pulmonary symptoms has been reported worldwide. Here we venture out to summarize the clinical profile, investigations, and radiological findings among patients with SARS-CoV-2-associated meningoencephalitis in the form of a systemic review. This review was carried out based on the existing PRISMA (Preferred Report for Systematic Review and Meta analyses) consensus statement. The data for this review was collected from four databases: Pubmed/Medline, NIH Litcovid, Embase, and Cochrane library and Preprint servers up till 30 June 2020. Search strategy comprised of a range of keywords from relevant medical subject headings which includes "SARS-COV-2," "COVID-19," and "meningoencephalitis." All peer reviewed, case-control, case report, pre print articles satisfying our inclusion criteria were involved in the study. Quantitative data was expressed in mean ± SD, while the qualitative date in percentages. Paired t test was used for analysing the data based on differences between mean and respective values with a p < 0.05 considered to be statistically significant. A total of 61 cases were included from 25 studies after screening from databases and preprint servers, out of which 54 of them had completed investigation profile and were included in the final analysis. Clinical, laboratory findings, neuroimaging abnormalities, and EEG findings were analyzed in detail. This present review summarizes the available evidences related to the occurrence of meningoencephalitis in COVID-19.

Extra-motor manifestations in post-polio syndrome (PPS): fatigue, cognitive symptoms and radiological features.

BACKGROUND: There is a paucity of cerebral neuroimaging studies in post-polio syndrome (PPS), despite the severity of neurological and neuropsychological sequelae associated with the condition. Fatigue, poor concentration, limited exercise tolerance, paraesthesia and progressive weakness are frequently reported, but the radiological underpinnings of these symptoms are poorly characterised. OBJECTIVE: The aim of this study is to evaluate cortical and subcortical alterations in a cohort of adult polio survivors to explore the anatomical substrate of extra-motor manifestations. METHODS: Thirty-six patients with post-polio syndrome, a disease-control group with amyotrophic lateral sclerosis patients and a cohort of healthy individuals were included in a prospective neuroimaging study with a standardised clinical and radiological protocol. Validated clinical instruments were utilised to assess mood, cognitive and behavioural domains and specific aspects of fatigue. Cortical thickness analyses, subcortical volumetry, brainstem segmentation and region-of-interest (ROI) white matter analyses were undertaken to assess regional grey and white matter alterations. RESULTS: A high proportion of PPS patients exhibited apathy, verbal fluency deficits and reported self-perceived fatigue. On ROI analyses, cortical atrophy was limited to the cingulate gyrus, and the temporal pole and subcortical atrophy were only detected in the left nucleus accumbens. No FA reductions were noted to indicate white matter degeneration in any of the lobes. CONCLUSIONS: Despite the high incidence of extra-motor manifestations in PPS, only limited cortical, subcortical and white matter degeneration was identified. Our findings suggest that non-structural causes, such as polypharmacy and poor sleep, may contribute to the complex symptomatology of post-polio syndrome.

The effects of examiner fatigue on the diagnostic accuracy of dental radiographs.

OBJECTIVES: The aim of the study was to find out whether and to what extent the performance of dentists regarding diagnostic evaluation of dental radiographs is influenced by symptoms of fatigue. MATERIALS AND METHODS: Over a period of 40 minutes, 21 dentists evaluated a database of 96 randomly selected, infinitely repeating intraoral dental radiographs for the presence of periapical radiolucencies. Both before and after, participants were asked to assess their subjective fatigue using the Swedish Occupational Fatigue Inventory (SOFI), Visual Analogue Scale (VAS), and Numerical Rating Scale (NRS). Diagnostic accuracy was analyzed using the Receiver Operating Characteristics (ROC) method. Furthermore, the correlation between diagnostic accuracy and radiographic experience, image viewing time, and level of training was also evaluated. RESULTS: The study showed that despite increasing fatigue, the diagnostic accuracy of the examiners remained consistent with an average AUC value of 0.768 ± 0.091. Within the 40-min reporting period, no statistically significant fluctuations were found. The diagnostic accuracy varied depending on the radiographic experience: with many years of radiographic experience, the diagnostic accuracy increased. At the same time, the older study participants with greater radiographic experience became less tired compared to younger study participants during the examination. CONCLUSIONS: Although an increase in fatigue was observed during the 40-min examination, the diagnostic accuracy of the doctors remained constant. CLINICAL RELEVANCE: Due to the high workload which needs to be handled in a limited time, medical and dental professionals have reached a certain level of exposition to stress that can lead to physical fatigue. However, the increasing fatigue should not negatively influence the work of the doctors. The study shows that the radiodiagnostic accuracy remained the same.

Brain anatomical correlates of fatigue in multiple sclerosis.

Fatigue is one of the most debilitating symptoms in patients with multiple sclerosis (MS). Despite its clinical significance, the aetiology and pathophysiology of MS-related fatigue are not well understood. Current evidence and understanding of the neuroanatomical underpinnings of MS-related fatigue are reviewed in this article. The aims of this paper are to (1) review the findings of previous structural neuroimaging studies on MS-related fatigue and summarize consistent findings regarding brain circuitry associated with fatigue in MS, (2) contextualize these findings with the neurochemistry of the relevant circuits and (3) discuss future perspectives with regard to impact on fatigue management of MS patients and methodological challenges towards improved understanding of fatigue pathogenesis. The detailed understanding of the neuroanatomical underpinnings of fatigue might contribute to the identification of novel treatment targets and factors determining treatment resistance to drugs used in current clinical practice.

Fatigue in multiple sclerosis: The role of thalamus.

Fatigue is very common in multiple sclerosis (MS) and is often considered as its most disabling symptom. Over the last 20 years, an increasing number of studies have evaluated the pathogenetic bases of MS-related fatigue. Converging evidence from neurophysiology and neuroimaging research suggests that a dysfunction in a cortico-subcortical pathway, centered on thalamus, is involved in the pathogenesis of fatigue. However, type and significance of such dysfunction remain unknown, and some studies reported an increase in the activity and connectivity within the thalamic network, whereas others suggested its reduction. Hereby, we review the results of neuroimaging studies supporting the different hypotheses about the role of thalamic network in the pathophysiology of MS-related fatigue and discuss limitations and shortcomings of available data, highlighting the key challenges in the field and the directions for future research.

Phosphorus magnetic resonance spectroscopy and fatigue in multiple sclerosis.

Fatigue stands among the most debilitating multiple sclerosis (MS) manifestations. Several pathophysiological mechanisms have been proposed at its origin. However, unmet needs still exist, and further investigations are required to better understand and manage this complaint. A new imaging modality-the phosphorous magnetic resonance spectroscopy (31P-MRS)-might help studying fatigue by allowing the measurement of energy metabolites of various cerebral regions. Therefore, this work aimed to explore the association between fatigue and brain energy status. Thirty MS patients with progressive disease forms completed the study. Their sociodemographic and clinical data including fatigue and disability scores [i.e., Fatigue Severity Scale (FSS) and Expanded Disability Status Scale (EDSS)] were collected. 31P-MRS spectra of (1) bilateral frontoparietal area and (2) centrum semiovale normal appearing white matter (NAWM) were obtained. Percentages of phosphocratine and ß-adenosine triphosphate (ß-ATP) were calculated. FSS scores were found to be directly correlated with the frontoparietal ß-ATP % (p < 0.05). However, there were no significant correlations between FSS scores and NAWM energy metabolites or clinical data (i.e., age, EDSS scores or disease duration). These findings point toward the existence of a link between fatigue severity and the amount of cerebral ATP metabolites. Such a link might reflect either a high production or low utilization of ATP, both of which were paralleled with increased fatigue perception. While the former would be due to a redistribution of ion channels along demyelinated axons and subsequent changes in mitochondrial activity; the latter could be interpreted in the light of neuronal loss which would lead to a decrease in ATP utilization and accumulation of its metabolites.

Neural and dopaminergic correlates of fatigue in Parkinson's disease.

Fatigue is one of the most common non-motor symptoms in Parkinson's disease (PD). Despite its clinical importance, there are few studies on the cause or mechanism of fatigue. Our aim was to find brain areas related to fatigue and to explore the association between striatal dopaminergic dysfunction and fatigue. We consecutively screened forty-seven patients with de novo PD from 2012 to 2017 and enrolled 32 patients. The gray matter volumes, white matter tracts, and striatal dopaminergic activity between PD without fatigue and with fatigue were compared. The correlation between fatigue and striatal dopaminergic activity was also analyzed. Our data did not show any significant difference in gray matter volume between PD without fatigue and with fatigue (familywise error [FWE] corrected p > 0.05) but revealed significantly higher mean fractional anisotropy (FA) values for all analyzed white matter tracts in PD with fatigue (false discovery rate [FDR] corrected p < 0.05), except left cingulum-hippocampus (CH), right superior longitudinal fasciculus, and right longitudinal fasciculus temporal part (FDR corrected p > 0.06); lower mean diffusivity (MD) values for all analyzed white matter tracts in PD with fatigue (FDR corrected p < 0.05), except in the left CH and uncinate fasciculus (FDR corrected p > 0.05). The mean radial diffusivity (RD) values, except for the left CH (FDR corrected p = 0.0576), were also significantly lower (FDR corrected p < 0.05). There was no difference in dopaminergic deficits between PD without fatigue and PD with fatigue (p > 0.50). The alteration of the white matter tract may reflect the degree of fatigue in PD. This is not true of the gray matter and striatal dopaminergic activity. These results show the possibility that white matter changes can be used as a biomarker for fatigue.

The Role of Multimodality Imaging in Monitoring Disease Activity and Therapeutic Response to Tocilizumab in Giant Cell Arteritis.

INTRODUCTION: Giant cell arteritis (GCA) is a large vessel (LV) vasculitis, mainly affecting elder patients. Monitoring GCA activity during tocilizumab (TCZ) treatment is an unmet need, since low serum levels of C-reactive protein (CRP) during treatment may underestimate disease activity. To date, few data are available on the role of different imaging techniques in monitoring GCA activity and response to treatment. We report herein a cohort of GCA patients treated with TCZ and followed up with multimodal imaging. Patients and Methods. We collected clinical, laboratory, and imaging data of 11 GCA patients treated with TCZ 162 mg subcutaneously every week. Disease activity was assessed at baseline and within 12 months from the start of treatment using different imaging techniques such as color Doppler ultrasonography (CDUS), magnetic resonance imaging/angiography (MRI/MRA), computed tomography angiography (CTA), and/or positron emission tomography (PET). RESULTS: Four patients were affected by cranial and 7 by LV-GCA. All patients were treated with oral glucocorticoids (GCs) (mean dose 55.68 mg ± 8.19 of prednisone or equivalent) in combination with TCZ. Treatment was preceded in 5 cases by 3 intravenous boluses of 1000 mg methylprednisolone. A significant decrease of the mean dose of oral GCs was observed between baseline and the last follow-up visit (4.65 ± 3.69 mg) (p = 0.003). TCZ treatment significantly decreased erythrocyte sedimentation rate (p < 0.01) and CRP levels (p < 0.01). At follow-up (mean 8.18 ± 3.63 months), all patients were in clinical and serological remission. Moreover, PET, CDUS, MRI/MRA, and CTA did not show any LVV finding. CONCLUSIONS: Our study highlights TCZ efficacy in inducing GCA remission and its steroid-sparing effect. We highlighted a reliability of imaging procedures in the evaluation of disease activity and treatment response. A close disease monitoring with imaging techniques should be taken into account in GCA patients during TCZ treatment.

White matter hyperintensities increases with traumatic brain injury severity: associations to neuropsychological performance and fatigue.

Objective: To examine the prevalence of white matter hyperintensities (WMHs) in patients with traumatic brain injury (TBI) as compared to healthy controls, and to investigate whether there is an association between WMH lesion burden and performance on neuropsychological tests in patients with TBI.Methods: A total of 59 patients with TBI and 27 age- and gender-matched healthy controls underwent thorough neuropsychological testing and magnetic resonance imaging. The quantification of WMH lesions was performed using the fully automated Lesion Segmentation Tool.Results: WMH lesions were more common in patients with TBI than in healthy controls (p = .032), and increased with higher TBI severity (p = .025). Linear regressions showed that WMH lesions in patients with TBI were not related to performance on any neuropsychological tests (p > .05 for all). However, a negative relationship between number of WMH lesions in patients with TBI and self-assessed fatigue was found (r = - 0.33, p = .026).Conclusion: WMH lesions are more common in patients with TBI than in healthy controls, and WMH lesions burden increases with TBI severity. These lesions could not explain decreased cognitive functioning in patients with TBI but did relate to decreased self-assessment of fatigue after TBI.

Progressive resistance exercise training and changes in resting-state functional connectivity of the caudate in persons with multiple sclerosis and severe fatigue: A proof-of-concept study.

Fatigue is one of the most disabling symptoms of multiple sclerosis (MS). While progressive resistance training (PRT) has been shown to reduce fatigue in persons with MS, it is not clear why these reductions occur. One hypothesis is that PRT may induce functional changes to the caudate, a region highly implicated in MS fatigue. The aim of the current study was to study the effects of PRT on overall fatigue impact and resting-state functional connectivity of the caudate in persons with MS reporting severe fatigue. Participants were semi-randomly assigned to either a 16-week home-based PRT (n = 5) or stretching control (n = 5) condition. Both groups demonstrated reductions in overall fatigue impact (main effect of time: F = .84, d = .65). Significant group × time interactions were found, with the PRT group demonstrating post-training increases in functional connectivity between the caudate and left inferior parietal (F = 66.0, p < .001), bilateral frontal (both p < .001), and right insula (F = 21.8, p = .002) regions compared to the stretching group. Furthermore, greater post-training increases in functional connectivity between the caudate and left inferior parietal region were associated with greater decreases in cognitive fatigue (r = -.52) specifically. This study provides initial evidence for the caudate as a potential neural substrate for the beneficial effects of PRT on fatigue in persons with MS.